Search Results (52)

Colorectal cancer (CRC) is a prevalent and lethal malignancy worldwide. Despite extensive research, core genes for diagnosis and prognosis in CRC remain to be fully elucidated. This study aims to identify novel gene biomarkers for CRC diagnosis and prognosis based on the GEO and TCGA datasets. Integration of TCGA and GEO datasets revealed 197 common differentially expressed genes (DEGs) between CRC tumor and normal samples. Functional enrichment analysis implicated these DEGs in biological processes and signaling pathways critical to CRC progression, including cell cycle regulation and nuclear division. Protein–protein interaction (PPI) network analysis identified 17 hub genes from DEGs, including TROAP, CDKN3, CDCA3, UBE2C, CEP55, KIF11, CDC20, CCNA2, MCM4, CKS2, POLE2, MAD2L1, CCNB1, PTTG1, TPX2, TOP2A, and DLGAP5. All 17 hub genes demonstrated high diagnostic value (AUC > 0.85), including CCNB1 (AUC = 0.944). Based on the Cox proportional hazards regression, an 8-gene prognostic signature (CLCA1, CCNB1, TPM2, MMP3, AOC3, CRYAB, CA4, GUCA2A) effectively stratified patients by survival risk, with a 5-year AUC of 0.71. In vitro, CCNB1 knockdown triggered cell cycle arrest, thereby suppressing the proliferation of colorectal cancer cells. This study validated CCNB1 as a dual-purpose biomarker for CRC diagnosis and favorable prognosis, highlighting its potential utility in clinical management. Full article

Background: Monkeypox (MPX), caused by the Monkeypox virus (MPOX) of the Orthopoxvirus genus, has re-emerged as a significant global health threat. Once confined to Central and West Africa, the 2022–2025 multi-country outbreaks, predominantly caused by Clade IIb, demonstrated sustained human-to-human transmission and global spread. Objective: This review summarizes current knowledge on MPX virology, epidemiology, clinical presentation, and diagnostic technologies, with a focus on innovations supporting rapid and field-deployable detection in resource-limited settings. Methods: The recent literature (2019–2025), including peer-reviewed studies, WHO and Africa CDC reports, and clinical guidelines, was critically reviewed. Data were synthesized to outline key developments in diagnostic methodologies and surveillance approaches. Results: MPX comprises two genetic clades: Clade I (Congo Basin) and Clade II (West African), which differ in virulence and transmission. Clade IIb is associated with sexual and close-contact transmission during recent outbreaks. Clinical manifestations have shifted from classic disseminated rash to localized anogenital lesions and atypical or subclinical infections. RT-PCR remains the diagnostic gold standard, while emerging assays such as loop-mediated isothermal amplification (LAMP), recombinase polymerase amplification (RPA), and CRISPR/Cas-based platforms show promise for rapid point-of-care (POC) testing. Complementary serological tools, including ELISA and lateral flow assays, enhance surveillance and immune profiling. Conclusions: The resurgence of MPX highlights the urgent need for accessible, sensitive, and specific diagnostic platforms to strengthen surveillance and outbreak control, especially in endemic and resource-constrained regions. Full article

Strawberries are important cash crops. Traditional manual picking is costly and inefficient, while automated harvesting robots are hindered by field challenges like stem-leaf occlusion, fruit overlap, and appearance/maturity variations from lighting and viewing angles. To address the need for accurate cross-maturity fruit identification and keypoint detection, this study constructed a strawberry image dataset covering multiple varieties, ripening stages, and complex ridge-cultivation field conditions: MSRBerry. Based on the YOLO11-pose framework, we proposed DHN-YOLO with three key improvements: replacing the original C2PSA with the CDC module to enhance subtle feature capture and irregular shape adaptability; substituting C3K2 with C3H to strengthen multi-scale feature extraction and robustness to lighting-induced maturity/color variations; and upgrading the neck into a New-Neck via CA and dual-path fusion to reduce feature loss and improve critical region perception. These modifications enhanced feature quality while cutting parameters and accelerating inference. Experimental results showed DHN-YOLO achieved 87.3% precision, 88% recall, and 78.6% mAP@50:95 for strawberry detection (0.9%, 1.6%, 5% higher than YOLO11-pose), and 83%, 87.5%, 83.6% for keypoint detection (1.9%, 2.1%, 4.6% improvements). It also reached 71.6 FPS with 15 ms single-image inference. The overall performance of DHN-YOLO also surpasses other mainstream models such as YOLO13, YOLO10, DETR and so on. This demonstrates DHN-YOLO meets practical needs for robust strawberry and picking point detection in complex agricultural environments. Full article

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a genetically distinct lineage from healthcare-associated MRSA (HA-MRSA), often producing Panton-Valentine leukocidin (PVL) and causing severe skin and soft tissue infections (SSTIs) in otherwise healthy individuals. Methods: We describe five cases of PVL-positive CA-MRSA SSTIs admitted to the Infectious Diseases Unit of the University Hospital “Paolo Giaccone,” Palermo, Italy, between 2024 and 2025. Case inclusion followed the CDC criteria for CA-MRSA. Microbiological identification was performed using MALDI-TOF mass spectrometry, and antimicrobial susceptibility testing followed EUCAST standards. PVL gene presence was confirmed by polymerase chain reaction. Results: Clinical management included surgical drainage, systemic antibiotic therapy, and decolonization of both patients and close contacts. Long-acting lipoglycopeptides (oritavancin or dalbavancin) were evaluated as therapeutic options to achieve clinical resolution. Conclusions: PVL-positive CA-MRSA infections are characterized by recurrence, intrafamilial clustering, and frequent therapeutic failure with standard oral agents. Effective management requires an integrated approach combining prompt surgical drainage; systemic therapy, preferably including long-acting lipoglycopeptides; and comprehensive decolonization of all close contacts. Full article

Incorporating cyclodextrins (CDs) into ionically crosslinked polysaccharide matrices offers a promising strategy for developing well-defined, safe-by-design and biocompatible carrier systems with tunable rheological properties. In this study, β-cyclodextrin (β-CD) was functionalized with citric acid (CDC) and maleic anhydride (CDM) using solvent-free synthesis to improve compatibility with alginate hydrogels. The modified CDs were characterized by FTIR, ¹H NMR, DLS, zeta potential, and MS, confirming successful esterification (4.0 and 3.4 –OH substitution for CDC and CDM, respectively) and stable aqueous dispersion. Rheological measurements showed that native CD accelerated gelation (within approximately 30 s), while CDC and CDM delayed crosslinking (by 2 to 13 min) and reduced gel strength, narrowing the linear viscoelastic range to 0.015–0.089% strain due to competition between polycarboxylated CDs and alginate chains for Ca²⁺ ions. Vibrational prilling produced alginate microbeads with diameters of 800–1000 µm and a simultaneous increase in size and CD concentration. Hydrogels demonstrated high CD retention (>80% after 28 h) and slightly greater release of CDC and CDM than native CD. Overall, solvent-free modification of CDs with citric and maleic acids provides a sustainable approach to tailoring the gelation kinetics, viscoelasticity, and release behavior of alginate-based hydrogels, offering a versatile, food- and health-compliant platform for controlled delivery of bioactive compounds. Full article

The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion and migration. It upregulated key growth factors (EGF, VEGF-A, IGF, TGF-β, and HGF), indicating the activation of regenerative signaling. Additionally, DOCDA increased the expression of genes related to focal adhesion and cytoskeletal regulation (ITGB1, ITGA4, FAK, SRC, RHOA, CDC42, RAC1, and paxillin), supporting enhanced cellular motility and remodeling. Notably, DOCDA promoted stem-like properties in HaCaT cells, as shown by increased spheroid formation and elevated levels of the stemness markers ALDH1 and CD44. Target prediction and molecular docking identified the glucocorticoid receptor (GR) as the primary target of DOCDA, with a docking score of −7.7 kcal/mol. Network and pathway enrichment analysis revealed that GR-linked pathways were significantly associated with wound healing, including steroid hormone signaling, inflammation, immune responses, and cell migration. In vivo, the topical application of DOCDA led to over 70% wound closure in mice by day 5. These findings suggest that DOCDA is a steroid-like compound that accelerates wound healing and may serve as a potential agent in regenerative therapy. Full article

Psoriasis pathogenesis involves dysregulated immune responses, yet the role of protein prenylation (particularly PGGT1B-mediated geranylgeranylation) in macrophage-driven inflammation remains poorly understood. This study aims to explore the role and molecular mechanism of protein geranylgeranyltransferase type I subunit beta (PGGT1B) in the development of psoriasis. Myeloid cell-specific PGGT1B gene knockout mice were generated, and a mouse psoriasis model was established with imiquimod to study the role and mechanism of PGGT1B gene downregulation-induced macrophage activation in the pathogenesis of psoriasis. Bone marrow-derived macrophages (BMDMs) from wild-type and PGGT1B knockout mice were cultured and stimulated with resiquimod (R848) to simulate the immune microenvironment of psoriasis. In addition, the differentially expressed genes induced by PGGT1B knockout were analyzed using RNA-seq, and bioinformatics analysis was carried out to study the possible biological process of PGGT1B regulation. Finally, PMA-THP-1 was co-cultured with HaCaT cells to study the effect of PGGT1B deletion in macrophages on the proliferation and differentiation of keratinocytes. Bone marrow PGGT1B deficiency aggravated the psoriasis-like lesions induced by imiquimod in mice. In BMDMs with PGGT1B deficiency, the NF-κB signaling pathway was over-activated by R848, and the expressions of proinflammatory cytokines IL-1β, IL-6, and TNF-α were significantly increased. Activation of cell division cycle 42 (CDC42) may mediate the activation of the NF-κB pathway in PGGT1B-deficient BMDMs. PGGT1B deletion can promote the proliferation and inhibit the differentiation of HaCaT cells. Reduced PGGT1B levels can increase the expression of CDC42, which further activates NLRP3 inflammation in macrophages through NF-κB signaling, further aggravating the inflammatory state of psoriasis. Psoriasis-like lesions induced by IMQ are aggravated when PGGT1B expression is reduced in mouse bone marrow cells. A possible mechanism for this is that PGGT1B-deficient macrophages migrate to the epidermis more easily during psoriasis, which leads to the activation of Cdc42, NF-κB signaling, and NLRP3 inflammatory corpuscles. Full article

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic malignancies. Despite the remarkable improvement concerning treatment, late detection and resistance to clinically used chemotherapeutic agents remain major challenges. Trichostatin A (TSA), a histone deacetylase inhibitor, has been recognized as an effective therapeutic agent against PDAC by inhibiting proliferation, inducing apoptosis, and sensitizing PDAC cells to chemotherapeutic agents such as gemcitabine. Microgravity has become a useful tool in cancer research due to its effects on various cellular processes. This paper presents a deep molecular and proteomic analysis investigating cell growth, the modulation of cytokeratins, and proteins related to apoptosis, cellular metabolism, and protein synthesis after TSA treatment in simulated microgravity (SMG)-exposed PaCa44 3D cells. Our analysis concerns the effects of TSA treatment on cell proliferation: the impairment of the cell cycle with the downregulation of proteins involved in Cdc42 signaling and G1/G2- and G2/M-phase transitions. Thus, we observed modification of survival pathways and proteins related to autophagy and apoptosis. We also observed changes in proteins involved in the regulation of transcription and the repair of damaged DNA. TSA treatment promotes the downregulation of some markers involved in the maintenance of the potency of stem cells, while it upregulates proteins involved in the induction and modulation of the differentiation process. Our data suggest that TSA treatment restores the cell phenotype prior to simulated microgravity exposure, and exerts an intriguing activity on PDAC cells by reducing proliferation and inducing cell death via multiple pathways. Full article

The clinicopathological and molecular features of synchronous parathyroid carcinoma (PC) and thyroid carcinoma in a male patient are presented. At 11, he received mantle field radiotherapy for Hodgkin lymphoma. He had a 26-year adulthood history of recurrent nephrolithiasis treated five times with lithotripsy. At 52, he was referred to our clinic for hypercalcemia. Primary hyperparathyroidism was diagnosed (calcium: 3.46 mmol/L, parathormone: 150 pmol/L, preserved renal function, nephrolithiasis, and osteoporosis). Neck ultrasound revealed a 41 × 31 × 37 mm nodule in the left thyroid and smaller nodules in the right thyroid. Enlarged cervical lymph nodes were not observed. The large nodule was interpreted as parathyroid adenoma on 99Tc-pertechnetate scintigraphy/99Tc-MIBI scintigraphy with SPECT/CT. Total left-sided and subtotal right-sided thyroidectomy were performed. Histopathology confirmed locally invasive, low-grade PC (pT2; positive for parafibromin and E-cadherin, negative for galectin-3 and PGP9.5; wild-type expression for p53 and retinoblastoma protein; Ki-67 index 10%) and incidental papillary thyroid carcinoma (pT1b). Genetic profiling revealed no loss in CDC73, MEN1, CCND1, PIK3CA, CDH1, RB1, and TP53 genes. Deletions in CDKN2A, LATS1, ARID1A, ARID1B, RAD54L, and MUTYH genes and monosomies in nine chromosomes were identified. The tumor mutational burden and genomic instability score were low, and the tumor was microsatellite-stable. The thyroid carcinoma exhibited a TRIM24::BRAF fusion. Following surgery, the parathormone and calcium levels had normalized, and the patient underwent radioiodine treatment for thyroid cancer. The follow-up of 14 months was eventless. In summary, the clinical, laboratory, and imaging features of hyperparathyroidism taken together could have suggested malignancy, then confirmed histologically. The synchronous carcinomas were most likely caused by irradiation treatment diagnosed 41 years after exposure. It seems that the radiation injury initially induced parathyroid adenoma in young adulthood, which underwent a malignant transformation around age fifty. Full article

Objective: Cytoreductive surgery (CRS) is the most important treatment method that increases survival in advanced-stage ovarian cancer (OC) patients. However, complications after CRS are seen as a significant cause of morbidity and mortality. Preoperative risk assessment of patients is of great importance. In recent years, inflammatory markers have been the subject of many studies evaluating malignancy and surgical outcomes. Ca125, Neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Monocyte–lymphocyte ratio (MLR), systemic inflammation index (SII), and systemic inflammatory response index (SIRI) stand out as prognostic and predictive tools in malignancies. This study aims to evaluate the preoperative inflammatory markers in patients who underwent CRS for advanced-stage epithelial ovarian cancer and to investigate the predictive power of postoperative complications. Materials and Methods: This retrospective study examines patients who underwent CRS due to advanced-stage epithelial OC at Sakarya University Training and Research Hospital between 2014 and 2023. Postoperative complications of the patients were graded according to the Clavien–Dindo classification (CDC); Ca125, NLR, PLR, SII, SIRI and MLR values were calculated using preoperative laboratory data, and the predictive values of inflammatory markers were analysed with ROC curves. Results: A significant relationship was found between complications with CDC ≥ 3 and NLR, PLR, MLR, SII, and SIRI. The AUC value of SII was calculated as 0.740 (p < 0.001), NLR as 0.719 (p = 0.001), PLR as 0.668 (p = 0.011), and SIRI as 0.651 (p = 0.022). SII stands out as the marker with the highest predictive power. SII is a strong marker in predicting postoperative complications, especially in advanced-stage OC patients. Conclusions: It was shown that preoperative inflammation markers may be an effective method for predicting postoperative complications in advanced-stage OC patients undergoing CRS. These findings may contribute to optimising surgical management and reducing complications. In future studies, these markers should be evaluated in groups with more patients, and their predictive power should be investigated. Full article

Coronavirus disease 2019 is a multi-systemic syndrome that caused a pandemic. Proteomic studies have shown changes in protein expression and interaction involved in signaling pathways related to SARS-CoV-2 infections. Protein phosphatases play a crucial role in regulating cell signaling. In this study, we assessed the potential involvement of protein phosphatases and their associated signaling pathways during SARS-CoV-2 infection by conducting a meta-analysis of proteome databases from COVID-19 patients. We identified both direct and indirect interactions between human protein phosphatases and viral proteins, as well as the expression levels and phosphorylation status of intermediate proteins. Our analyses revealed that PPP2CA and PTEN are key phosphatases involved in cell cycle and apoptosis regulation during SARS-CoV-2 infection. We also highlighted the direct involvement of PPP2CA in the cell division throughout its interaction with CDC20 protein (cell division cycle protein 20 homolog). This evidence strongly suggests that both proteins play critical roles during SARS-CoV-2 infection and represent potential targets for COVID-19 treatment. Full article

Monoclonal antibody (mAb) and cell-based immunotherapies represent cutting-edge strategies for cancer treatment. However, safety concerns persist due to the potential targeting of normal cells that express reactive antigens. Therefore, it is crucial to develop cancer-specific mAbs (CasMabs) that can bind to cancer-specific antigens and exhibit antitumor activity in vivo, thereby reducing the risk of adverse effects. We previously screened mAbs targeting human epidermal growth factor receptor 2 (HER2) and successfully developed a cancer-specific anti-HER2 mAb, H₂Mab-250/H₂CasMab-2 (mouse IgG₁, kappa). In this study, we assessed both the in vitro and in vivo antitumor efficacy of the humanized H₂Mab-250 (humH₂Mab-250). Although humH₂Mab-250 showed lower reactivity to HER2-overexpressed Chinese hamster ovary-K1 (CHO/HER2) and breast cancer cell lines (BT-474 and SK-BR-3) than trastuzumab in flow cytometry, both humH₂Mab-250 and trastuzumab showed similar antibody-dependent cellular cytotoxicity (ADCC) against CHO/HER2 and the breast cancer cell lines in the presence of effector splenocytes. In addition, humH₂Mab-250 exhibited significant complement-dependent cellular cytotoxicity (CDC) in CHO/HER2 and the breast cancer cell lines compared to trastuzumab. Furthermore, humH₂Mab-250 possesses compatible in vivo antitumor effects against CHO/HER2 and breast cancer xenografts with trastuzumab. These findings highlight the distinct roles of ADCC and CDC in the antitumor effects of humH₂Mab-250 and trastuzumab and suggest a potential direction for the clinical development of humH₂Mab-250 for HER2-positive tumors. Full article

Mucinous epithelial ovarian cancer (mEOC) is a rare subtype of epithelial ovarian cancer, characterized by poor responses to standard platinum-based chemotherapy. Polo-like kinase 1 (PLK1) is a key regulator of mitosis and cell cycle progression and its inhibition has been recently identified as a target in mEOC. In this study, we aimed to identify further therapeutic targets in mEOC using a CRISPR/Cas9 library targeting 3015 genes, with and without treatment with onvansertib, a PLK1 inhibitor. We identified twelve genes associated with cell survival (ZC2HC1C, RPA2, KIN17, TUBG1, SMC2, CDC26, CDC42, HOXA9, TAF10, SENP1, MRPS31, and COPS2) and three genes (JUND, CARD9, and BCL2L2) in synthetic lethality with onvansertib treatment. We validated that SENP1 downregulation is important for the growth of mEOC cells through esiRNA interference and the use of a pharmacological inhibitor Momordin Ic. The downregulation of CARD9 and BCL2L2 combined with subtoxic doses of onvansertib interfered with mEOC cell growth. Interestingly, the combination of navitoclax, an inhibitor of BcL2 family members including BCL2L2, was synergistic in all four of the mEOC cell lines tested and substantially induced cell death through apoptosis. These data support the use of a combination of navitoclax and onvansertib as a new therapeutic strategy for mEOC. Full article

Background: Many factors contribute to the development and the progression of Multiple Sclerosis (MS), including Human Leukocyte Antigen (HLA) molecules. Some of them are considered as predisposing, like DRB1*15, DRB1*13, DRB1*03, DRB1*04, DQB1*06, DQB1*02, while HLA A2, HLA B44, DRB1*11, and DRB1*12 are rather considered as protective. Data about such associations in the Moroccan population remain unknown. The aim of this study was to determine the frequency of HLA class I (A and B) and II (DR and DQ) linked to Multiple Sclerosis (MS) in a healthy population from the South of Morocco. Materials and Methods: A cross-sectional study was carried out over the 2016–2023 period on 685 Moroccan healthy individuals, including 355 males and 330 females. Of the total sample tested, 685 underwent HLA class I typing, of which 305 also benefited from HLA class II typing. HLA class I typing was executed using the CDC (complement dependent cytotoxicity) technique (OneLambda™, Los Angeles CA, USA), and HLA class II typing was performed by either PCR-SSP (sequence-specific primer, OneLambda) or PCR-SSO (sequence-specific oligonucleotides) using the Luminex Xmap (Lifecodes, Immucor, Peachtree, Corners, GA, USA) system. Results: From different HLA molecules potentially predisposing to MS, our investigations showed that DRB1*03, DRB1*13, DRB1*15, DRB1*04, and DQB1*02 were observed in 19.2%, 15.8%, 13.31%, 12.7% and 31% respectively, while the frequency of those considered as protective, namely HLA-A2, HLA-B44, and HLA-DRB1*11 was 23.31%, 9.21% and 10.1% respectively. Conclusions: The findings of our study give evidence that among predisposing HLA class II molecules, DR allele groups were more prevalent, mostly DRB1*03, with also a high frequency of DQB1*06, while HLA-A2 marked the supposed protective specificities. These results need to be supported by complementary studies particularly in MS patients. Full article

Wood from reforestation gains market value due to its sustainable and legal origin. Planted forests in Brazil play a crucial role in economic, social and environmental aspects, with Eucalyptus and Pinus dominating the timber sector. However, non-majority species, such as those of the Khaya genus, have attracted great commercial interest due to the quality of their wood, being seen as an alternative to Brazilian mahogany. This study aimed to evaluate the biomass production of Khaya spp. stands and the nutrient uptake impacts in different harvesting scenarios. The research area is in Reserva Natural Vale (RNV) in Sooretama, Espírito Santo state, Brazil. The study was conducted 9.5 years after the planting of the Khaya spp. monoculture at a spacing of five m × five m, and the base fertilization consisted of 150 g of yoorin thermophosphate and 15 g of FTE BR 12 per seedling. The seedlings were of seminal origin, coming from different regions of Brazil and corresponding to three species: Kkaya grandifoliola C.DC (Belém-PA), Khaya ivorensis A. Chev. (Linhares-ES) and Khaya senegalensis A. Juss. (Poranguatu-GO). K. senegalensis exhibited the highest percentage of bark, while K. ivorensis was found to have the highest percentage of leaves. The biomass of the stems and branches did not vary by species. The relative biomass proportions had the following order: branches > stems > bark > leaves. The stocks of Ca and Mg were higher for K. grandifoliola, exceeding those for K. senegalensis (22.1%) for Ca and for K. ivorensis (42.3%) for Mg. The lowest nutrient uptake occurred in the scenario in which only the stem was removed, with averages of 44.17, 10.43, 21.93, 52.59 and 9.97 kg ha⁻¹ for N, P, K, Ca and Mg, respectively. Compared to total biomass harvesting, this represents a reduction in export levels by 91.34% for N, 79.31% for P, 94.66% for K, 94.29% for Ca and 93.28% for Mg. The nutrient uptake assessment demonstrated that more conservative harvest scenarios resulted in lower nutrient losses, indicating the importance of forest management practices that prioritize soil and nutrient conservation. In summary, the findings of this study provide a solid basis for the sustainable management of Khaya spp., highlighting implications for productivity and nutrient dynamics on a small or medium scale. Full article